MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Liver Anatomy and Physiology Where is the Liver? • Upper right quadrant, beneath the diaphragm • Largest internal organ • Weighs ~ 1500 grams Anatomy of the Liver • Consists of 2 lobes divided by falciform ligament • There is no known difference between the lobes Liver • Vascular organ – Hepatic artery • Supplies O2 rich blood from heart to liver • Provides 20-30% of blood supply to liver – Portal vein • Supplies nutrient rich blood from the digestive tract • Provides 70-80% of blood to liver From Aorta From GI tract Microscopic Anatomy of the Liver • Lobules make up the liver – 6-sided structure – Central vein with portal triads at each corner – Triad contains a hepatic artery, portal vein and bile duct surrounded by connective tissue – Function in metabolic and excretory actions Microscopic Anatomy of Liver • Cell types – Hepatocytes • 70% of volume of liver • Regenerative • Perform major functions of liver – Kupffer cells • Macrophages acting as phagocytes Biochemical Function of the Liver • • • • • Excretion/Secretion Synthesis Detoxification Storage Immunologic Excretory System • Excretion of bile acids, cholesterol, bilirubin • Begins at the bile canaliculi, enters hepatic ducts, then to common hepatic & bile duct Excretion/Secretion • Liver processes and excretes – Bile • Water, electrolytes, phospholipids, bile salts or acids, bile pigments, cholesterol , heme waste products, and other substances from blood • 3L produced/day • 1L excreted/day • Functions • Bile acids needed for fat absorption • Mechanism to remove cholesterol and waste • Bilirubin is the principal pigment in bile Bilirubin Metabolism Metabolism of Bilirubin • Around 126 days, RBCs are phagocytized and hgb released • Hgb broken down into: – Heme • Converted to bilirubin – Globin • Broken into amino acids and recycled – Iron • Bound by transferrin and returned to iron stores in the liver or bone marrow Metabolism of Bilirubin • Bilirubin – Bound by albumin and taken to liver (unconjugated or indirect bilirubin) • Water insoluble • Can not be removed from body • Once at the liver, unconjugated bilirubin flows into sinusoidal tissue and albumin releases it • Ligandin, picks up the unconjugated bilirubin and presents it to glucuronic acid • In the liver it becomes conjugated with the help of UDP-glucuronyl transferase – Water soluble – Combines with gallbladder secretions and expelled into intestines Metabolism of Bilirubin • Intestinal bacteria degrade conjugated bilirubin to form urobilinogen – 80% of urobilinogen formed is oxidized to stercobilin and excreted in feces, giving stool the brown color – 20% of urobilinogen formed • Absorbed by extrahepatic circulation to be recycled through liver and re-excreted • Enters systemic circulation to be filtered by kidney and excreted in urine Synthesis • Synthesize many biological compounds – Carbohydrates • Metabolism important – Uses glucose for its own cellular energy – Circulates glucose to peripheral tissue – Stores glucose as glycogen • Major player in maintaining stable glucose concentration due to glycogenesis, glycogenolysis and gluconeogenesis Synthesis – Lipids • Liver gathers free fatty acids from diet and breaks them down to Acetyl- CoA to form triglycerides, phospholipids or cholesterol • Converts insoluble lipids to soluble forms • 70% of cholesterol produced by the liver – Proteins • Almost all proteins made in the liver • Exceptions are immunoglobulins and hgb Detoxification • Liver serves as a gatekeeper between the circulation and absorbed substances – First pass: every substance absorbed in GI tract passes through liver • Detoxification includes drugs and poisons, and metabolic products like ammonia, alcohol, and bilirubin • 3 mechanisms – Binds material reversibly to inactivate – Chemically modify compound for excretion – Drug metabolizer for detox of drugs and poisons Storage • • • • Glycogen Vitamins Iron Blood Immunologic • Phagocytosis of bacteria • IgA secretion References • Biofortified. (2012). Retrieved from http://www.biofortified.org/2010/03/glowing-phagocytosis/ • Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins. • http://www.livercancer.com/liver_anatomy.html • Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson .